Chromosome aberrations and cell death by ionizing radiation: Evolution of a biophysical model
Chromosome aberrations and cell death by ionizing radiation: Evolution of a biophysical model
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DOI：
10.1016/j.radphyschem.2016.06.009
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发表时间：
2016-11-01
影响因子：
2.9
通讯作者：
Carante, Mario P.
中科院分区：
文献类型：
--
作者：
Ballarini, Francesca;Carante, Mario P.
该手稿总结和讨论了各种版本的辐射损伤生物物理模型，实施为蒙特卡罗模拟代码，最初开发的染色体畸变，随后扩展到细胞死亡。这个扩展版本被称为BIANCA（细胞死亡和染色体畸变的生物物理分析）。根据基本假设，复杂的双链断裂（称为“簇损伤”或CL）产生独立的染色体游离末端，在阈值距离d内的错误重新连接（或未重新连接）导致染色体畸变，并且“致死畸变”（即，双着丝粒加上环加上大缺失）导致克隆原性细胞死亡。每戈伊和每个细胞的CL平均数是可调节的参数。虽然在BIANCA中阈值距离d是第二个参数，但在随后的版本中，称为BIANCA II，d已被固定为两个相邻间期染色体区域之间的平均距离，并引入了一个新的参数f来表示染色体自由端未重接概率。将各种模型版本获得的染色体畸变和细胞存活的模拟剂量反应曲线与文献实验数据进行比较。这样的比较提供了一些悬而未决的问题，包括能量沉积聚集在nm和gm水平的作用，染色体游离端保持未重新连接的概率，以及染色体畸变和细胞死亡之间的关系的迹象。虽然BIANCA和BIANCA II提供的细胞存活曲线与人和仓鼠成纤维细胞存活数据基本一致，但BIANCA II允许更好地复制双着丝粒、环和缺失。此外，BIANCA II对d采用的方法与文献中报告的估计数更加一致。在对畸变和存活数据进行测试后，BIANCA II被应用于研究质子SOBP用于治疗意大利卡塔尼亚眼黑色素瘤的辐射有效性的深度依赖性。再现了AG01522细胞在不同深度的存活情况，并预测了V79细胞的存活情况。对于这两种细胞系，模拟还预测了染色体畸变的产量，其中一些可以被视为正常组织风险的指标。(C)2016爱思唯尔有限公司版权所有。
The manuscript summarizes and discusses the various versions of a radiation damage biophysical model, implemented as a Monte Carlo simulation code, originally developed for chromosome aberrations and subsequently extended to cell death. This extended version has been called BIANCA (Biophysical ANalysis of Cell death and chromosome Aberrations). According to the basic assumptions, complex double-strand breaks (called "Cluster Lesions", or CLs) produce independent chromosome free-ends, mis-rejoining within a threshold distance d (or un-rejoining) leads to chromosome aberrations, and "lethal aberrations" (i.e., dicentrics plus rings plus large deletions) lead to clonogenic cell death. The mean number of CLs per Gy and per cell is an adjustable parameter. While in BIANCA the threshold distance d was the second parameter, in a subsequent version, called BIANCA II, d has been fixed as the mean distance between two adjacent interphase chromosome territories, and a new parameter, f, has been introduced to represent the chromosome free-end un-rejoining probability. Simulated dose-response curves for chromosome aberrations and cell survival obtained by the various model versions were compared with literature experimental data. Such comparisons provided indications on some open questions, including the role of energy deposition clustering at the nm and the gm level, the probability for a chromosome free-end to remain un-rejoined, and the relationship between chromosome aberrations and cell death. Although both BIANCA and BIANCA II provided cell survival curves in general agreement with human and hamster fibroblast survival data, BIANCA II allowed for a better reproduction of dicentrics, rings and deletions considered separately. Furthermore, the approach adopted in BIANCA II for d is more consistent with estimates reported in the literature. After testing against aberration and survival data, BIANCA II was applied to investigate the depth-dependence of the radiation effectiveness for a proton SOBP used to treat eye melanoma in Catania, Italy. The survival of AG01522 cells at different depths was reproduced, and the survival of V79 cells was predicted. For both cell lines, the simulations also predicted yields of chromosome aberrations, some of which can be regarded as indicators of the risk to normal tissues. (C) 2016 Elsevier Ltd. All rights reserved.